vaccine therapy in treating patients with stage iv or relapsed malignant melanoma

Conditions: Melanoma

Summary: rationale: vaccines made from peptides may make the body build an immune response to kill tumor cells. purpose: phase i/ii trial to study the effectiveness of vaccine therapy in treating patients who have stage iv, or relapsed malignant melanoma.

objectives: * determine the safety of administering mart-1 peptide-pulsed dendritic cells to patients with stage iv or relapsed malignant melanoma. * determine the immunological and clinical responses in this patient population after this therapy. outline: this is a dose-escalation study. patients undergo leukapheresis between days -14 to -8. mononuclear cells are isolated, used to generate dendritic cells (dc), and then pulsed with mart-1 peptide. patients are vaccinated with mart-1 peptide-pulsed dc either iv or intradermally on days 0, 14, and 28. cohorts of 3-6 patients receive escalating doses of mart-1 peptide-pulsed dc until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. patients are followed until death. projected accrual: a total of 18-24 patients will be accrued for this study.

Eligibility criteria:
inclusion criteria: * adults over the age of 18 with malignant melanoma. * hla-a2.1 positive and express mart-1, as assessed by either rt-pcr or by immunohistochemistry * tumor stages t3n0m0 or greater are eligible for this trial according to the following: 1. i (\<.75 to 1.5 mm or clark level iii-t1-2n0m0-)-not eligible 2. ii (1.5 to 4 mm or level iv-t3n0m0-)-eligible 3. iii (limited nodal metastasis involving one regional lymph node basin, or fewer than 5 in-transit metastasis -txn1m0-)-eligible 4. iv (advanced regional metastasis -txn2m0- or any distant metastasis -txnxm1-)-eligible 5. relapsed melanoma-eligible * patients previously treated with any form of therapy for either metastatic, relapsed or primary melanoma are eligible for this trial, provided that previous treatment was completed \>30 days prior to enrollment * both male and females may be enrolled. premenopausal females must have a negative pregnancy test prior to treatment * karnofsky performance status greater than or equal to 70 percent * no previous evidence of class 3 or greater new york heart association cardiac insufficiency or coronary artery disease * no previous evidence of opportunistic infection * a minimum of 30 days must have elapsed since the completion of prior chemotherapy, immunotherapy or radiation therapy * adequate baseline hematological function as assessed by the following laboratory values within 30 days prior to study entry (day -30 to 0): 1. hemoglobin \>9.0 g/dl 2. platelets \> 100000/mm3 3. wbc \> 3000/mm3 4. absolute neutrophil count \> 1000/mm3 * positive skin test to common antigens (tetanus and candida) * ability to give informed consent exclusion criteria: * lactating females and females of child-bearing potential must have negative serum beta-hcg pregnancy test * acute infection: any acute viral, bacterial, or fungal infection which requires specific therapy. acute therapy must have been completed within 14 days of prior to study treatment * hiv-infected patients * acute medical problems such as ischemic heart or lung disease that may be considered an unacceptable anesthetic or operative risk * patients with any underlying conditions which would contraindicate therapy with study treatment (or allergies to reagents used in this study) * patients with organ allografts * uncontrolled cns metastasis. patients with cns metastasis will be eligible if they have received cns irradiation to control local tumor growth

Keywords: stage iv melanoma recurrent melanoma